Cell Volume Regulation in Chondrocytes

Lewis, Rebecca; Feetham, Claire H.; Barrett‐Jolley, Richard

doi:10.1159/000335847

Cited by 63 publications

(72 citation statements)

References 135 publications

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“…Finally, a sodium channel known to be functional in chondrocytes was studied (SCNN1A). 26 When quantitative PCR was performed on each of these genes to validate the microarray data, it was found that each ion channel mRNA was upregulated in OA sfMPCs compared to normal sfMPCs with the exception of KCNMA1, which had no change (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

et al. 2016

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Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.

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Section: Resultsmentioning

confidence: 99%

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

et al. 2016

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“…It is, however, reasonable to suggest that the overall capacity of these channels is dictated, at least in part, by their level of expression. Furthermore, the level of expression of these channels has been shown to differ in pathological cartilage, although whether this is causative or a result of the disease is unclear (24). In either case, altered expression could lead to progression of the disease and increased degeneration of the cartilage.…”

Section: Discussionmentioning

confidence: 99%

Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Hdud

Mobasheri

Loughna

2014

American Journal of Physiology-Cell Physiology

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Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BK Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. Am J Physiol Cell Physiol 306: C1050 -C1057, 2014. First published March 26, 2014 doi:10.1152/ajpcell.00287.2013.-The metabolic activity of articular chondrocytes is influenced by osmotic alterations that occur in articular cartilage secondary to mechanical load. The mechanisms that sense and transduce mechanical signals from cell swelling and initiate volume regulation are poorly understood. The purpose of this study was to investigate how the expression of two putative osmolyte channels [transient receptor potential vanilloid 4 (TRPV4) and largeconductance Ca 2ϩ -activated K ϩ (BKCa)] in chondrocytes is modulated in different osmotic conditions and to examine a potential role for MAPKs in this process. Isolated equine articular chondrocytes were subjected to anisosmotic conditions, and TRPV4 and BK Ca channel expression and ERK1/2 and p38 MAPK protein phosphorylation were investigated using Western blotting. Results indicate that the TRPV4 channel contributes to the early stages of hypo-osmotic stress, while the BK Ca channel is involved in responding to elevated intracellular Ca 2ϩ and mediating regulatory volume decrease. ERK1/2 is phosphorylated by hypo-osmotic stress (P Ͻ 0.001), and p38 MAPK is phosphorylated by hyperosmotic stress (P Ͻ 0.001). In addition, this study demonstrates the importance of endogenous ERK1/2 phosphorylation in TRPV4 channel expression, where blocking ERK1/2 by a specific inhibitor (PD98059) prevented increased levels of the TRPV4 channel in cells exposed to hypo-osmotic stress and decreased TRPV4 channel expression to below control levels in iso-osmotic conditions (P Ͻ 0.001).cartilage; chondrocyte; mitogen-activated protein kinase; osmotic; transient receptor potential vanilloid 4 ARTICULAR CARTILAGE covers the ends of bones in diarthrodial joints to provide protection from shearing and compressive forces generated secondary to joint articulation. Cartilage consists of extracellular matrix (ECM) and chondrocytes (3,30). ECM is composed mainly of collagen type II and proteoglycan (PG), as well as other small protein and glycoprotein components. Chondrocytes are the only resident cells found in articular cartilage. Their metabolic activity is strongly influenced by environmental factors, including soluble mediators, ECM composition, and dynamic changes induced by mechanical loading (13,46). Mechanical loading of articular cartilage induces fluid flow, mechanical membrane deformation, hydrostatic pressure, and osmotic stress (45).The osmolarity of the tissue fluid that bathes chondrocytes in the cartilage ECM is different from that of most other tissues and typically exceeds 380 mosM (47). The presence of polyanionic PG molecules in the ECM attracts cations, such as Na ϩ

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“…In this case, cells restore their original volume by activation of regulatory volume increase (RVI) mechanisms. Both RVD and RVI have mostly been investigated in mammalian cells [10], but also in cells of lower vertebrates and invertebrates [11,12,13]. With regard to invertebrates, we have previously demonstrated cell volume regulation in response to both hyposmotic and hypertonic stress in isolated nematocytes, and suggested the involvement of transport systems for multiple ions (namely Cl - and K + for RVD and Na + for RVI) and aquaporins in this regulation [9,14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Sea Water Acidification Affects Osmotic Swelling, Regulatory Volume Decrease and Discharge in Nematocytes of the JellyfishPelagia noctiluca

Morabito

Marino

Lauf³

et al. 2013

Cell Physiol Biochem

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Background: Increased acidification/P_CO2 of sea water is a threat to the environment and affects the homeostasis of marine animals. In this study, the effect of sea water pH changes on the osmotic phase (OP), regulatory volume decrease (RVD) and discharge of the jellyfish Pelagia noctiluca (Cnidaria, Scyphozoa) nematocytes, collected from the Strait of Messina (Italy), was assessed. Methods: Isolated nematocytes, suspended in artificial sea water (ASW) with pH 7.65, 6.5 and 4.5, were exposed to hyposmotic ASW of the same pH values and their osmotic response and RVD measured optically in a special flow through chamber. Nematocyte discharge was analyzed in situ in ASW at all three pH values. Results: At normal pH (7.65), nematocytes subjected to hyposmotic shock first expanded osmotically and then regulated their cell volume within 15 min. Exposure to hyposmotic ASW pH 6.5 and 4.5 compromised the OP and reduced or totally abrogated the ensuing RVD, respectively. Acidic pH also significantly reduced the nematocyte discharge response. Conclusion: Data indicate that the homeostasis and function of Cnidarians may be altered by environmental changes such as sea water acidification, thereby validating their use as novel bioindicators for the quality of the marine environment.

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Cell Volume Regulation in Chondrocytes

Cited by 63 publications

References 135 publications

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Sea Water Acidification Affects Osmotic Swelling, Regulatory Volume Decrease and Discharge in Nematocytes of the JellyfishPelagia noctiluca

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Cell Volume Regulation in Chondrocytes

Cited by 63 publications

References 135 publications

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Sea Water Acidification Affects Osmotic Swelling, Regulatory Volume Decrease and Discharge in Nematocytes of the JellyfishPelagia noctiluca

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Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes